Fetal cardiovascular and breathing responses to an adenosine A2a receptor agonist in sheep.
CGS-21680 (CGS), a highly selective adenosine A2a receptor agonist, may excite the fetal carotid bodies. This study was designed to determine 1) whether CGS stimulates fetal breathing and 2) whether sinoaortic denervation abolishes CGS-induced tachycardia. In eight intact fetuses (> 0.8 term), intra-arterial CGS infusion (6 micrograms.min-1.kg estimated fetal wt-1) increased mean arterial PCO2 by 3-7 Torr, reduced fetal arterial PO2 by 2-5 Torr, and produced a mild metabolic acidemia. Heart rate increased from 154 +/- 7 (control) to 249 +/- 12 beats/min, but mean arterial pressure was not significantly affected. CGS initially increased the frequency, amplitude, and incidence of fetal breathing, but this hyperpnea was followed by prolonged respiratory depression that was not reversed with blockade of adenosine A1 receptors. Denervation of both carotid bodies together with interruption of the vagi abolished the hyperpnea without altering the respiratory depression or the maximum rise in heart rate. We conclude that CGS induces 1) tachycardia by a mechanism independent of the peripheral arterial chemoreceptors, 2) hyperpnea by stimulating peripheral adenosine A2a receptors, and 3) respiratory depression by activating central A2a receptors.
Koos
B J
BJ
Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, University of California Los Angeles School of Medicine 90095-1740, USA.
Chau
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002344:Carotid Body / Q000196:embryology; D002628:Chemoreceptor Cells / Q000502:physiology; D004569:Electroencephalography; D004585:Electrooculography; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D006340:Heart Rate, Fetal / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009121:Muscle Denervation; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010627:Phenethylamines / Q000494:pharmacology*; D011247:Pregnancy; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D012119:Respiration / Q000187:drug effects*; D012756:Sheep; D012849:Sinoatrial Node / Q000196:embryology / Q000294:innervation*; D014132:Trachea / Q000196:embryology; D014630:Vagus Nerve / Q000196:embryology
D000959:Antihypertensive Agents; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D002245:Carbon Dioxide; D000241:Adenosine; D010100:Oxygen